tbuckley/cabot-search huggingface dataset:
AB0649 Myositis Specific Antibodies - Who orders them and what are the results? A retrospective audit of two large referral centers
Authors: S. Shan, A. Foote, L. Schachna, M. Mian
Journal: Annals of the Rheumatic Diseases (2022)

Background Idiopathic inflammatory myopathies are a group of disorders associated with myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) (1). MSA and MAA are helpful in classifying clinical syndromes with both treatment and prognostic implications (2). Ordering of MSA and MAA has increased in recent years. We report the hospital services that ordered MSA and MAA and follow-up investigations performed in two large referral centers in Melbourne, Australia. Objectives To explore and investigate the testing patterns of MSA and subsequent follow up. Methods We identified all patients who underwent MSA and MAA testing between January 1 2019 and December 31 2020. Relevant demographic and clinical data were obtained by chart review. Results Over the 2-year study period, 294 MSA tests were ordered, alongside 275 ANA and 266 ENA. Of these, 60 (20.4%) were positive and 9 (3.1%) tested positive to more than one MSA. Interstitial lung disease (ILD) was the most common extra-muscular manifestation, 42 (14.2%) had muscle disease manifestations. Respiratory (41%), rheumatology (24%) and neurology (15%) were the top three specialties ordering the most MSA, with the highest proportion of positive MSA originating from rheumatology (38.5%). The rheumatology service was involved in 131 (41.0%) of the MSA ordered as the primary treating unit or as a consultation service. Anti-Scl100 was the most common MSA (n=10, 15.6%). Among the 60 patients with positive MSA, 39 (65%) was given a definitive diagnosis, 13 (21.7%) underwent MRI of muscles, 10 (16.7%) open muscle biopsy, and 5 (8.3%) a skin biopsy. Thirty-two (53.3%) of MSA positive patients underwent high-resolution CT chest; 26 (81.3) % had findings suggestive of a fibrotic process and 12 (20.0%) had a formal diagnosis of ILD. A cancer screen was performed in 23 (38.3%) of the MSA positive patients and no malignancy was identified within the cohort. Conclusion Among MSA studies performed in two large centers, 20.4% of results were positive. Respiratory ordered the most numerous tests predominantly to evaluate ILD, a higher proportion of tests recommended by the rheumatology service was positive. References [1]Targoff IN. Update on myositis-specific and myositis-associated autoantibodies. Curr Opin Rheumatol. 2000;12(6):475-81. [2]Betteridge Z, McHugh N. Myositis-specific autoantibodies: an important tool to support diagnosis of myositis. J Intern Med. 2016;280(1):8-23. Disclosure of Interests None declared
AB1214 VITAMIN D SUPPLEMENTATION IN FIBROMYALGIA: A SYSTEMATIC REVIEW
Authors: H. Sousa, A. S. Pinto, J. F. Ferreira
Journal: Annals of the Rheumatic Diseases (2022)

Background Fibromyalgia (FM) is a chronic disease characterized by diffuse pain associated with high levels of fatigue whose intensity is very variable. Similar symptoms are found in patients with low levels of vitamin D, a vitamin that behaves like a hormone with multiple receptors spread in several tissues. Although its role in the pathophysiology of FM remains unclear many studies point to a correlation between vitamin D deficiency and FM symptoms severity. (1) Objectives Conduct a systematic review of the literature to determine the value of vitamin D supplementation in fibromyalgia. Methods Medline, EMBASE, and Cochrane databases were searched, from January 2000 to January 2022, using the descriptors “Fibromyalgia”, “Fatigue” and “Vitamin D.” Randomized and clinical control trials including FM patients in whom supplementation of vitamin D was made were selected. Data comprised sociodemographic description, diagnosis criteria, fibromyalgia symptoms, Fibromyalgia Impact Questionnaire (FIQ), short-form 36 (SF36), and vitamin D supplementation protocol was collected. Results Of the initial 2480 articles, 4 were eligible for final analysis. One did not observe any significant improvement in FIQ scores with vitamin D supplementation. The remaining three observed significant improvements in SF-36 and FIQ scores but to different extents. One only demonstrated improvements in specific components of the SF-36, also demonstrating improvements concerning morning fatigue. Another demonstrates improvements in all SF-36parameters, except for pain level. Lastly, other observed improvements in the scores of both FIQ and SF-36 scales. Conclusion Our review shows conflicting results regarding the role of using vitamin D supplementation in the quality of life of patients with FM(S). These results can be explained by different supplementations protocols and also different baseline levels of vitamin D for which it was decided to supplement. Nevertheless, vitamin D supplementation appears to have a benefit in fatigue and quality of life in FM patients. Larger studies, which last longer and have a more uniform supplementation protocol, are needed to confirm the results of this review. References [1]Makrani, A. H., Afshari, M., Ghajar, M., Forooghi, Z., &amp; Moosazadeh, M. (2017). Vitamin D and fibromyalgia: a meta-analysis. The Korean journal of pain, 30(4), 250–257. https://doi.org/10.3344/kjp.2017.30.4.250 Disclosure of Interests None declared
AB0057 REGULATION OF TYPE I INTERFERON SIGNATURE BY VGLL3 IN THE FIBROBLAST-LIKE SYNOVIOCYTES OF RHEUMATOID ARTHRITIS
Authors: Y. Du, S. M. Dai
Journal: Annals of the Rheumatic Diseases (2022)

Background The upregulation of interferon (IFN)-stimulated genes (ISGs) induced by type I IFNs (namely type I IFN signature) in RA patients had implications in early diagnosis and prediction of therapy responses. However, factors that modulate the type I IFN signature in RA are largely unknown. Objectives To explore the involvement of VGLL3, a homologue of the vestigial-like gene in Drosophila and a putative regulator of the Hippo pathway, in the modulation of the type I IFN signature in RA. Methods FLS were isolated from RA and osteoarthritis patients. Expression of VGLL3 in the synovial tissues and FLS was analyzed by immunohistochemistry and PCR. RNA sequencing was performed in RA-FLS upon VGLL3 overexpression. The expression of ISGs was examined by PCR and Western blotting. Results VGLL3 was upregulated in the RA synovium and RA-FLS compared to OA. Overexpression of VGLL3 promoted the expression of ISGs in RA-FLS. The expression of STAT1 and MX1 was also upregulated in RA synovium compared to OA. The expression of STAT1 and MX1 was associated with the expression of VGLL3 in RA and OA patients. VGLL3 promoted the IRF3 activation, IFN-β1 expression, and IFN-β1 autocrine signaling in RA-FLS. VGLL3 also modulated the expression of the Hippo pathway molecules WWTR1 and AMOTL2, which mediated the regulation of IRF3 activation and IFN-β1 production by VGLL3 in RA-FLS. Conclusion VGLL3 drives the IRF3-induced IFN-β1 secretion in RA-FLS by inhibiting WWTR1 expression and subsequently promotes the type I IFN signature expression through autocrine IFN-β1 signaling. Acknowledgements We would like to thank Prof. Si-feng Chen (Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China) for scientific advice and technical assistance. Disclosure of Interests None declared
Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix
Authors: Emily J. Kay, Karla Paterson, Carla Riera-Domingo, David Sumpton, J. Henry M. Däbritz, Saverio Tardito, Claudia Boldrini, Juan R. Hernandez-Fernaud, Dimitris Athineos, Sandeep Dhayade, Ekaterina Stepanova, Enio Gjerga, Lisa J. Neilson, Sergio Lilla, Ann Hedley, Grigorios Koulouras, Grace McGregor, Craig Jamieson, Radia Marie Johnson, Morag Park, Kristina Kirschner, Crispin Miller, Jurre J. Kamphorst, Fabricio Loayza-Puch, Julio Saez-Rodriguez, Massimiliano Mazzone, Karen Blyth, Michele Zagnoni, Sara Zanivan
Journal: Nature Metabolism (2022)

Abstract Elevated production of collagen-rich extracellular matrix is a hallmark of cancer-associated fibroblasts (CAFs) and a central driver of cancer aggressiveness. Here we find that proline, a highly abundant amino acid in collagen proteins, is newly synthesized from glutamine in CAFs to make tumour collagen in breast cancer xenografts. PYCR1 is a key enzyme for proline synthesis and highly expressed in the stroma of breast cancer patients and in CAFs. Reducing PYCR1 levels in CAFs is sufficient to reduce tumour collagen production, tumour growth and metastatic spread in vivo and cancer cell proliferation in vitro. Both collagen and glutamine-derived proline synthesis in CAFs are epigenetically upregulated by increased pyruvate dehydrogenase-derived acetyl-CoA levels. PYCR1 is a cancer cell vulnerability and potential target for therapy; therefore, our work provides evidence that targeting PYCR1 may have the additional benefit of halting the production of a pro-tumorigenic extracellular matrix. Our work unveils new roles for CAF metabolism to support pro-tumorigenic collagen production.
AB1250 TOFACITINIB IS A SAFE AND EFFECTIVE TREATMENT OPTION FOR JUVENILE IDIOPATHIC ARTHRITIS
Authors: N. Prabu, V. Petciappan, G. Anand, S. Ram, A. Kumar
Journal: Annals of the Rheumatic Diseases (2022)

Background The management of juvenile idiopathic arthritis(JIA) is often constrained by the limited number of oral drugs available. Whether JAK inhibitors would add a much needed therapeutic armamentarium in this regard needs to be explored. Objectives To assess the safety and efficacy of tofacitinib in juvenile idiopathic arthritis (JIA) patient who were prescribed during the period January 2021 to December 2021. Methods It’s a retrospective study of JIA patients who were prescribed tofacitinib during the period Jan 21 to Dec 21 with minimum of 3 months’ follow-up after prescribing tofacitinib. The demographics,details of medications,investigations parameters and any adverse events were noted. Results There were a total of 35 patients who were given tofacitinib during this period. Male is to female ratio is 25:10, mean age of 12.91(4.81) yrs., the mean disease duration was 58.6 months. Enthesitis related arthritis(ERA) was the commonest seen in 12, followed by oligo articular in 10, polyarticular in 7 and systemic onset in 6. In the ERA group 10 were HLA B27 +VE, of the oligo articular 6 were ANA +VE, in the polyarticular one was RF +ve. Out of the 35,14 were already on biologicals (tocilizumab and anti TNFs). Tofacitinib was stopped in 8 patients during this period, 5 as they achieved remission, 2 with no response and one because of itching and abdominal pain. There were no documented infections. There was significant reduction in the inflammatory markers (ESR, CRP), leucocyte count and platelet count. Before tofa After tofa p value Methotrexate in mg (week) mean(stdev) 9.64(1.94) 8.88(3.34) 0.66 Steroid in mg mean (stdev) 3(2.35) 2.8(1.8) 0.91 Leucocyte count mean(stdev) 11242(1858) 7884(1471) 0.005 Platelet count in lakhsMean(stdev) 4.51(0.48) 3.37(0.82) 0.017 ESR mm/1hr 57.75(17.25) 30.83(11.48) 0.009 CRP mg/L 25.36(10.9) 12.36(7.97) 0.05 Conclusion Tofacitinib seems to be a promising drug in the management of JIA with good safety profile and efficacy. References [1] Brunner HI, Schanberg LE, Kimura Y et al. New medications are needed for children with juvenile idiopathic arthritis. Arthritis Rheumatol. 2020; 72: 1945-1951. Disclosure of Interests None declared
POS0433 POTENTIAL THERAPEUTIC EFFECTS OF NARINGENIN ON RA THROUGH SUPPRESSING P2X7R/NLRP3 MEDIATED PYROPTOSIS BY TARGETING ESR
Authors: H. Wang, Y. Zhang
Journal: Annals of the Rheumatic Diseases (2022)

Background Naringenin (NAR), a partial agonist on estrogen receptor, is naturally occurring flavonoids in grapes and grapefruits. We previously reported that NAR in patients with Rheumatoid arthritis (RA) have changed significantly [1]. However, the role and mechanism of action of NAR in RA remain unclear. Objectives This study aimed to determine the roles and mechanisms of NAR on RA and provides a basis for NAR to become a potential therapeutic agent for RA. Methods This study employed bovine type II collagen-induced arthritis (CIA) rats, in vitro mononuclear cells (MNCs) as models to explore the potential therapeutic effects and mechanisms of NAR on RA. Results Rats following NAR injections showed significantly alleviated CIA, while the proportion of NK cells decreased. After CIA rats were injected with both NAR and NK cells, the rats remained joint inflammation. NAR decreased the proportion of NK cells in RA MNCs. However, NAR did not directly affect the NK cell activation and their cytokine production. NAR suppress pyroptosis in THP-1 cells (Figure 1). The NAR activate the ESR1 in macrophage. NAR significantly increased histone deacetylase 1 gene (HDAC1) activation in macrophage. NAR significantly increased P2X7R expression and decreased NLRP3 expression in macrophage. Figure 1. Effect of NAR on RA in vitro and in vivo. A The chemical structures of NAR and Estrogen. B Flow cytometry assay of NK cells in MNCs with treatment of NAR. C The morphology of THP-1 cells with treatment of NAR. D Joint inflammation of CIA rats with treatment of NAR and NK cells. E The expression level of pyroptosis -related protein was tested by western blot (WB). F Pattern diagram explaining therapy mechanism of NAR to RA. Conclusion NAR has therapeutic effects for CIA and RA through suppressing P2X7R/NLRP3 mediated pyroptosis by targeting ESR. References [1]Wang H, Fang K, Wang J, Chang X. Metabolomic analysis of synovial fluids from rheumatoid arthritis patients using quasi-targeted liquid chromatography-mass spectrometry/mass spectrometry. Clinical and experimental rheumatology. 2021;39(6):1307-1315. Acknowledgements Natural Science Foundation of Shandong Province (ZR2021QH329). Disclosure of Interests None declared.
AB0418 INCREASED THROMBOEMBOLIC RISK OF JAK INHIBITORS AFTER SWITCHING FROM BIOLOGIC DMARDs IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Y. Eun, G. H. Seo, S. Y. Kang, S. Lee, H. Kim, H. S. Cha, E. M. Koh, J. Lee
Journal: Annals of the Rheumatic Diseases (2022)

Background Safety concerns regarding JAK inhibitors have grown since the ORAL surveillance trial reported that their use was associated with an increase in major adverse cardiovascular events compared to TNF inhibitors. However, real-world data on the association between JAKi and thromboembolic events are sparse. Objectives We compared the incidence of thromboembolic events (TEs) before and after switching to Janus kinase inhibitors (JAKi) from biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). Methods Among patients with a diagnostic code for RA taking bDMARDs, patients who switched to JAKi or another bDMARD between March 2015 and December 2020 were included in this self-controlled case series study. The outcome was the occurrence of TEs. The incidence rate ratios (IRRs) for TEs in the period after switching to JAKi or another bDMARD compared with the period before switching were calculated based on an assumed Poisson distribution. Results There were 1,150 and 2,254 patients who switched to JAKi and another bDMARD, respectively. The mean follow-up duration was 4.5 ± 1.8 years. In the JAKi group, the IRR for TE after drug switching was 1.56 (95% confidence interval [CI] 1.22–1.98, P &lt; 0.001) compared with the period before the drug switch; in the bDMARD group, the IRR was 1.16 (95% CI 0.98–1.38, P = 0.079). Conclusion Switching from bDMARDs to JAKi was associated with an increase in TE incidence in RA patients in a real-world setting. Disclosure of Interests None declared
AB0621 Characteristics of Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis With Severe Peripheral Neuropathy.
Authors: S. Ishigaki, M. Akiyama, Y. Kaneko
Journal: Annals of the Rheumatic Diseases (2022)

Background Peripheral neuropathy is one of major manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and has a significant impingement on patients’ quality of life. 1,2 Objectives The aim of this study was to clarify clinical features of AAV patients with peripheral neuropathy and identify risk factors for severe motor neuropathy. Methods All consecutive patients with active, treatment-naïve AAV who were admitted to our hospital between April, 2012 and October, 2021 were reviewed. Patients were divided into two groups according to the presence or absence of peripheral neuropathy, and their baseline clinical characteristics were compared. Results A total of 76 patients (microscopic polyangiitis, MPA, n=37, granulomatosis with poly angiitis, GPA, n=24, eosinophilic GPA, EGPA, n=15) were included in the study. Among them, 28 patients (36.8%) had peripheral neuropathy including 12 with MPA, 4 with GPA, and 12 with EGPA. The clinical characteristics of all patients with peripheral neuropathy were younger age (66.0 years versus 74.5 years, p &lt;0.05) and showed higher white blood cell counts (11500/μL versus 8800/μL, p &lt;0.05), higher blood eosinophil counts (788.5/μL versus 139.0/μL, p &lt;0.05), higher creatinine clearance (77.3 mL/min versus 56.3 mL/min, p &lt;0.05), higher levels of serum immunoglobulin (Ig)E (660 IU/mL versus 125 IU/mL, p &lt;0.05), and IgG4 (361.5 mg/dL versus 84.0 mg/dL, p &lt;0.05). In patients with EGPA, the most susceptible type to peripheral neuropathy, 80% of the patients had peripheral neuropathy. Comparison between patients with EGPA with peripheral neuropathy and those without demonstrated significantly younger age (56.0 years versus 80.0 years, p &lt;0.05) and higher blood eosinophil counts (7832/μL versus 2340/μL, p &lt;0.05) were characteristic for the presence of peripheral neuropathy. Patients with EGPA with motor neuropathy (n=8) showed higher white blood cell counts (26850//μL versus 8650//μL, p &lt;0.05) and higher blood eosinophil counts (13134//μL versus 3436//μL, p &lt;0.05) compared with those with only sensory neuropathy (n=4). Conclusion Our current study has shown that patients with EGPA are more prone to peripheral neuropathy than patients with MPA or GPA. Severe motor neuropathy was observed only in patients with EGPA and associated with more intense eosinophilic inflammation. Our results suggest that molecular targeted therapy that improves eosinophilic inflammation such as anti-IL-5 therapy is beneficial for peripheral neuropathy. References [1]RUTGERS, Abraham; KALLENBERG, Cees GM. Peripheral neuropathy in AAV—when vasculitis hits a nerve. Nature Reviews Rheumatology , 2012, 8.3: 127-128. [2]NAKAZAWA, Daigo, et al. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nature Reviews Rheumatology , 2019, 15.2: 91-101. Disclosure of Interests None declared
AB1317 SERUM INTERLEUKIN 37 LEVELS IN FAMILIAL MEDITERRANEAN FEVER PATIENTS AND ASSOCIATION WITH CLINICAL FEATURES
Authors: A. Fincan, M. Kavutcu, N. Atas, H. Babaoglu, R. Bilici Salman, H. Satiş, D. Yildirim, M. A. Ozturk, H. Küçük, A. Tufan
Journal: Annals of the Rheumatic Diseases (2022)

Background Familial Mediterranean Fever (FMF) is the most common form of autoinflammatory diseases that is characterized by febrile episodes of serositis, arthritis and skin rash (1). Mutations in MEFV gene causes dysfunction of pyrin inflammasome, ultimately resulting in over-activation of Caspase-1 which is responsible for catalytic activation of interleukin (IL)-1 beta and gasdermin-D (2). IL-37 is also one of the IL-1 cytokines activated by caspase-1 acting as natural inhibitor of inflammation (3). Objectives IL-37 has pathogenetic roles for certain inflammatory diseases. We aimed to investigate serum IL-37 levels and its relationship with clinical and laboratory features of disease. Methods 58 adult patients diagnosed with FMF according to Tel Hashomer criteria were included. Thirty subjects were served as healthy control subjects. Demographic, genetic, clinical and laboratory features and treatment responses of patients were recorded. Twenty-nine patients were colchicine responsive whereas 29 were colchicine refractory. Serum IL-37 levels were measured by ELISA from blood samples obtained at attack free periods. Results Peritonitis was the most common attack type (81%) followed by fever (80%) and arthritis (67%). There was no difference between FMF patients and healthy subjects for their serum IL-37 levels. A negative correlation was found between IL-37 values ​​and erythrocyte sedimentation rate in FMF patients (r: -0,31; p:0.015). IL -37 level was found to be significantly lower in patients who suffer from arthritis (median [IQR] 119 [396] ng/L vs 53 [164] ng/L, p= 0.03), myalgia (147 [364] ng/L vs 53 [84] ng/L, p= 0.05) or skin rash (102 [360] ng/L vs 54 [130] ng/L, p= 0.05) compared to those who did not have these attacks. Conclusion Although there was no difference in serum IL-37 levels between FMF patients and healthy subjects, IL-37 seem to be associated with musculoskeletal and skin attacks of FMF. Further research is needed to determine whether IL-37 have relationships with other features of FMF such as spondyloarthritis and febril myalgia. References [1]El-Shanti H, Majeed HA, El-Khateeb M. Familial mediterranean fever in Arabs.Lancet. 2006;367(9515):1016–24. [2]Kanneganti A, Malireddi RKS, Saavedra PHV, Vande Walle L, Van Gorp H, Kambara H, Tillman H, Vogel P, Luo HR, Xavier RJ, Chi H, Lamkanfi M. GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever. J Exp Med. 2018 Jun 4;215(6):1519-1529. doi: 10.1084/jem.20172060 [3]Nieman DC, Ferrara F, Pecorelli A, Woodby B, Hoyle AT, Simonson A, Valacchi G. Postexercise Inflammasome Activation and IL-1β Production Mitigated by Flavonoid Supplementation in Cyclists. Int J Sport Nutr Exerc Metab. 2020 Sep 15:1-9. doi: 10.1123/ijsnem.2020-0084. Acknowledgements No financial support is obtained from any company Disclosure of Interests None declared